The transdermal route of parenteral administration offers numerous advantages over other administration routes. Methods and systems to administer drugs through the skin are widely known in the field of pharmacy. Transdermal administration typically utilizes passive transdermal systems (e.g., Transdermal Therapeutic Systems, TTS), which supply the organism with defined amounts of pharmaceutical actives via diffusion through the skin.
Specifically the transdermal transport of actives dissolved in a liquid is problematical in that a gel or a sponge cloth or nonwoven carrier material containing the active has to be kept separate from the backing layer, together with which the active in the TTS is fixed to the skin, since prolonged storage stability is otherwise not ensured or since the active may have to be kept cooled or since it may be sensitive to oxidation. The user of a medicated patch then has to transfer the active-containing carrier material, having moved it from its usually sealed and hence liquid-impervious package by removing the closure film, to the backing layer of a transdermal therapeutic system (TTS) and fix it thereon. All the while, however, because of the risk of germ transfer, the user should ideally not touch the active-containing carrier material with his or her fingers and should ideally also not use any additional aids to effect the transfer.
The usual procedure is therefore to place the TTS backing layer face down onto the upwardly opened package of active-containing carrier material and press the carrier material against the TTS backing layer. When the TTS is thereafter removed again from the opened package, the active-containing carrier material is left adhering to the TTS backing layer, combining therewith to form the TTS in the actual sense, but this does not always happen reliably. Oftentimes or at least occasionally, the carrier material with the active is simply left behind in the package.
One place where this problem occurs is with the method of iontophoresis, which is deployed when passive transdermal drug delivery is but very inefficient for certain types of drugs. Ionized medicaments in particular are often unable to passively pass through the skin in a therapeutically effective amount.
The process of iontophoresis was originally described by LeDuc in 1908 and even earlier in US-222,276 (1879) and US-486,902 (1892). Iontophoresis has since found commercial use in the transdermal delivery of ionically charged therapeutically active molecules such as pilocarpine, lidocaine, dexamethasone, lidocaine and fentanyl.
Iontophoresis in general is a delivery method based on the fundamental principle that the application of electrical current makes available external energy to increase the ability of a drug to permeate through the membranes of the skin by improving the passage of active-ingredient ions through the skin.
When ions bearing a positive charge (cationic actives, for example) are placed into or underneath the anode of an iontophoretic system, the application of a current will cause an impulse to be exerted on these ions which moves them away from the anode in the direction of the electrical field toward the cathode, arranged in the immediate vicinity of the skin. During this process, the transportation of the cationic drug through the skin is improved or facilitated.
Iontophoresis can be carried out with various forms of active pharmaceutical ingredients, most favorably with those which have an electrical charge and which, in an electrical field, thus develop the ability to cross barriers (e.g., the skin).
A typical iontophoretic drug delivery system comprises an electrolytic electrical system composed of an anode and a cathode, which are placed on different—preferably adjacent—skin areas of a patient, each electrode being connected via a wire to an external power supply. In general, this is a microprocessor-controlled electrical instrument. Such types of devices are known, including systems of extremely simple design (e.g., U.S. Pat. No. 5,685,837 or 6,745,071) or else more complex systems of which a person skilled in the art has in-principle knowledge. Iontophoretic transdermal systems for lidocaine and fentanyl have already been successfully launched in the U.S. A very particularly detailed description of a system for delivering drugs by means of iontophoresis is found in WO 2012/071175.
U.S. Pat. No. 5,558,633 relates that iontophoresis devices are particularly suitable for the delivery of medicaments from a liquid or from gelled aqueous formulations. However, in such devices, the iontophoretic administration of pharmaceutical actives can be greatly impaired by the presence of “background” electrolytes (see for instance Luzardo-Alvarez, A., et al., Proceedings of the International Symposium on Controlled Release of bioactive Materials (2000), 27th Ed., pp. 159 to 160). Regarding the design of iontophoretic devices, moreover, there is a want of pharmaceutical gels or liquids which do not themselves have a disruptive effect as “background” counterions.
Various still existing deficiencies notwithstanding, iontophoresis has proved useful as a delivery method in all those cases where a conventional TTS does not suffice to ensure the rapid administration of a therapeutically effective dose of such an active ingredient. However, there is the inherent risk with iontophoresis that side-effects such as skin irritation, skin reddening, burning or else skin necrosis can occur in particular on increasing the current strength or on practicing the iontophoretic treatment for a prolonged period. On the other hand, an increase in the current strength can be perfectly desirable for the administration of higher doses of therapeutic active, since the number of ions transported is directly proportional to the level of current flow per unit time.
The problem addressed by the present invention in view of the above was therefore that of providing a method whereby an active-containing carrier material can be reliably removed from its pack and fixed to the TTS backing layer for the purposes of subsequent application—whether with or without augmentation by iontophoresis—without this requiring the active-containing carrier material to be touched by hand or an additional aid being needed to effect the transfer.
US 2002/0019652 A1 discloses a patch for transcurtaneous electrical nerve stimulation (TENS). The TENS method is a non-invasive pain management method which in principle eschews pharmaceutical actives. In one embodiment, the patch comprises a reusable upper part which contains an electronics module and switches to turn the power supply on and off and adjust the current strength. The lower part is subdivided into three sections arranged side by side. The two outer sections serve as plus and minus electrodes and are intended for direct contact with the skin, while the center section consists with preference of sterile gauze material. The gauze material may contain an active. In a particular embodiment, the upper part as depicted in FIG. 3 contains a layer (70) of a magnetic polymer. The lower part (40) likewise contains a layer (86) of magnetic polymer at the upper side, as depicted in FIG. 4. The magnetic layers of the two parts can then adhere to each other. According to para [0023], the sterile gauze is absorbent in the region (80). It is thus supposed to absorb wound exudate or the like. In a further embodiment, the upper and lower parts are joined together by a hook and loop fastener (Velcro). The magnetic layer (70) of the upper part is then replaced by one half of the hook and loop fastener, and the magnetic layer (86) of the lower part by the other half.
WO 2012/071175 A1 discloses an iontophoretic patch in a two-part protective sleeve. The electrodes (22) and (24) are separated from the active-containing carrier material (42) or, respectively, (44) by a barrier film (52) or, respectively, (54). The ends (52a) and (54a) of the film project out of the protective sleeve (60a) and (60b). The barrier film is pulled out before use. Mechanical pressure on the protective sleeve puts the electrodes into direct contact with the active-containing carrier material. Before applying the iontophoretic patch, the protective sleeve is removed (see FIG. 5A to 5F). The separation of the electrodes from the active-containing carrier material is intended to extend the shelf life of the patch.